84,832 results match your criteria point mutations


Second Paediatric Strategy Forum for anaplastic lymphoma kinase (ALK) inhibition in paediatric malignancies: ACCELERATE in collaboration with the European Medicines Agency with the participation of the Food and Drug Administration.

Eur J Cancer 2021 Sep 15;157:198-213. Epub 2021 Sep 15.

Hospital for Sick Children, Toronto, Canada.

The first (2017) and sixth (2021) multistakeholder Paediatric Strategy Forums focused on anaplastic lymphoma kinase (ALK) inhibition in paediatric malignancies. ALK is an important oncogene and target in several paediatric tumours (anaplastic large cell lymphoma [ALCL], inflammatory myofibroblastic tumour [IMT], neuroblastoma and hemispheric gliomas in infants and young children) with unmet therapeutic needs. ALK tyrosine kinase inhibitors have been demonstrated to be active both in ALK fusion-kinase positive ALCL and IMT. Read More

View Article and Full-Text PDF
September 2021

Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy type 1 (STR1VE-EU): an open-label, single-arm, multicentre, phase 3 trial.

Lancet Neurol 2021 Oct;20(10):832-841

Novartis Gene Therapies, Cambridge, UK.

Background: Spinal muscular atrophy is a rare, autosomal recessive, neuromuscular disease caused by biallelic loss of the survival motor neuron 1 (SMN1) gene, resulting in motor neuron dysfunction. In this STR1VE-EU study, we aimed to evaluate the safety and efficacy of onasemnogene abeparvovec gene replacement therapy in infants with spinal muscular atrophy type 1, using broader eligibility criteria than those used in STR1VE-US.

Methods: STR1VE-EU was a multicentre, single-arm, single-dose, open-label phase 3 trial done at nine sites (hospitals and universities) in Italy (n=4), the UK (n=2), Belgium (n=2), and France (n=1). Read More

View Article and Full-Text PDF
October 2021

The mutagenic effect of tobacco smoke on male fertility.

Environ Sci Pollut Res Int 2021 Sep 18. Epub 2021 Sep 18.

College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.

Despite the association between tobacco use and the harmful effects on general health as well as male fertility parameters, smoking remains globally prevalent. The main content of tobacco smoke is nicotine and its metabolite cotinine. These compounds can pass the blood-testis barrier, which subsequently causes harm of diverse degree to the germ cells. Read More

View Article and Full-Text PDF
September 2021

Cypermethrin and ivermectin resistance in field populations of Rhipicephalus sanguineus sensu lato (Latrielle, 1806) collected from dogs in south India.

Vet Res Commun 2021 Sep 18. Epub 2021 Sep 18.

Department of Veterinary Parasitology, NTR College of Veterinary Science, Sri Venkateswara Veterinary University, Gannavaram, 521102, Andhra Pradesh, India.

The abuse of acaricides for control of Rhipicephalus sanguineus sensu lato ticks led to a strong selection pressure for acaricide resistance. Data on acaricide resistance in R. sanguineus s. Read More

View Article and Full-Text PDF
September 2021

AMPK S-sulfuration contributes to HS donors-induced AMPK phosphorylation and autophagy activation in dopaminergic cells.

Neurochem Int 2021 Sep 14:105187. Epub 2021 Sep 14.

Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, 215123, China. Electronic address:

Hydrogen sulfide (HS) serves as a neuromodulator and regulator of neuroinflammation. It is reported to be therapeutic for Parkinson's disease (PD) animal and cellular models. However, whether it affects α-synuclein accumulation in dopaminergic cells, the key pathological feature in PD, is poorly understood. Read More

View Article and Full-Text PDF
September 2021

Insulin-like growth factor-1 regulates the mechanosensitivity of chondrocytes by modulating TRPV4.

Cell Calcium 2021 Aug 31;99:102467. Epub 2021 Aug 31.

Biomedical Engineering, University of Delaware, Newark, DE, United States; Biomechanics and Movement Science Program, University of Delaware, Newark, DE, United States; Department of Biological Sciences, University of Delaware, Newark, DE, United States; Department of Biology, University of Michigan-Flint, Flint, MI, United States. Electronic address:

Both mechanical and biochemical stimulation are required for maintaining the integrity of articular cartilage. However, chondrocytes respond differently to mechanical stimuli in osteoarthritic cartilage when biochemical signaling pathways, such as Insulin-like Growth Factor-1 (IGF-1), are altered. The Transient Receptor Potential Vanilloid 4 (TRPV4) channel is central to chondrocyte mechanotransduction and regulation of cartilage homeostasis. Read More

View Article and Full-Text PDF

Directed evolution of Zymomonas mobilis sugar facilitator Glf to overcome glucose inhibition.

J Ind Microbiol Biotechnol 2021 Sep 16. Epub 2021 Sep 16.

School of Life Sciences, Arizona State University, Tempe, Arizona, USA.

Cellular import of D-xylose, the second most abundant sugar in typical lignocellulosic biomass, has been evidenced to be an energy-depriving process in bacterial biocatalysts. The sugar facilitator of Zymomonas mobilis, Glf, is capable of importing xylose at high rates without extra energy input, but is inhibited by D-glucose (the primary biomass sugar), potentially limiting the utility of this transporter for fermentation of sugar mixtures derived from lignocellulose. In this work we developed an E. Read More

View Article and Full-Text PDF
September 2021

Adjuvant therapy in non-small cell lung cancer: is targeted therapy joining the standard of care?

Expert Rev Anticancer Ther 2021 Sep 16. Epub 2021 Sep 16.

Center for Thoracic Oncology, Tisch Cancer Institute, Mount Sinai System & Icahn School of Medicine, Mount Sinai, New York, NY, USA.

Introduction: Surgical resection is the standard of care in non-small cell lung cancer (NSCLC) for early stage disease (stage I-IIIA). Despite the use of adjuvant chemotherapy, the 5- year overall survival (OS) rates remain low. In NSCLC with advanced stages (stage IV), tailored strategies have become the gold standard approach applying precision medicine thanks to the introduction of genomic analysis with next generation sequencing (NGS) and the development of targeted therapy and immunotherapy. Read More

View Article and Full-Text PDF
September 2021

A family of three with haemoglobin Cheverly: low oxygen saturation in stable patients.

J R Coll Physicians Edinb 2021 Sep;51(3):253-256

Sarawak General Hospital, Jalan Hospital, 93586, Kuching, Sarawak, Malaysia.

Haemoglobin (Hb) Cheverly is a rare, low oxygen affinity haemoglobinopathy. It is a result of point mutation at the 45 codon of the beta globin genes that leads to substitution of phenylalanine by serine. It is characterised by spuriously low peripheral oxygen saturation with normal arterial oxygen saturation. Read More

View Article and Full-Text PDF
September 2021

Cancer immunotherapy: Recent advances and challenges.

J Cancer Res Ther 2021 Jul-Sep;17(4):834-844

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.

Immunotherapy is a treatment that uses specific components of a person's immune system to fight diseases. This is usually done by stimulating or assisting one's immune system is attacking the offending agent - for instance, in the case of cancer - the target of immunotherapy will be cancer cells. Some types of immunotherapy are also called biologic therapy or biotherapy. Read More

View Article and Full-Text PDF
September 2021

Plant Mitochondria - Past, present and future.

Plant J 2021 Sep 16. Epub 2021 Sep 16.

Department of Biology, Lund University, SE-22362, Lund, Sweden.

The study of plant mitochondria started in earnest around 1950 with the first isolations of mitochondria from animal and plant tissues. The first 35 years were spent establishing the basic properties of plant mitochondria and plant respiration using biochemical and physiological approaches. A number of unique properties (compared to mammalian mitochondria) were observed: (i) The ability to oxidize malate, glycine and cytosolic NAD(P)H at high rates. Read More

View Article and Full-Text PDF
September 2021

Screening for hereditary transthyretin amyloidosis in Bulgaria.

Med Pharm Rep 2021 Aug 10;94(Suppl No 1):S8-S10. Epub 2021 Aug 10.

Clinic of Nervous Diseases, Alexandrovska University Hospital, Medical University - Sofia, Bulgaria.

Transthyretin amyloid (ATTR) amyloidosis is a rare disorder with an adult-onset defined by the accumulation of misfolded fibrils predominantly in peripheral nerves, the heart, and the digestive tract. The disease is characterized by two forms - hereditary (ATTRv) or acquired (ATTRwt). Various point mutations in the transthyretin gene induce the hereditary form of the disease. Read More

View Article and Full-Text PDF

Complete Response to Afatinib of an EGFR Exon 18 delE709_T710insD-Mutated Stage IV Lung Adenocarcinoma.

Eur J Case Rep Intern Med 2021 11;8(8):002749. Epub 2021 Aug 11.

Department of Pulmonology, Hôpital Erasme, Brussels, Belgium.

Introduction: Epidermal growth factor receptor (EGFR) mutations are frequently found in patients with lung adenocarcinomas, 90% being deletions in exon 19 or point mutation in exon 21. Three generations of tyrosine kinase inhibitors (TKIs) targeting EGFR mutations are available and have changed patient prognosis but less data is available on exon 18 mutations and their sensitivity to TKI therapy. Exon 18 delE709_T710insD accounts for 0. Read More

View Article and Full-Text PDF

Mutagenicity of carcinogenic heterocyclic amines in Salmonella typhimurium YG strains and transgenic rodents including gpt delta.

Genes Environ 2021 Sep 16;43(1):38. Epub 2021 Sep 16.

School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama, 703-8516, Japan.

Chemical carcinogens to humans have been usually identified by epidemiological studies on the relationships between occupational or environmental exposure to the agents and specific cancer induction. In contrast, carcinogenic heterocyclic amines were identified under the principle that mutagens in bacterial in the Ames test are possible human carcinogens. In the 1970s to 1990s, more than 10 heterocyclic amines were isolated from pyrolysates of amino acids, proteins, meat or fish as mutagens in the Ames test, and they were demonstrated as carcinogens in rodents. Read More

View Article and Full-Text PDF
September 2021

Mutations in the adenosine deaminase ADAR1 that prevent endogenous Z-RNA binding induce Aicardi-Goutières-syndrome-like encephalopathy.

Immunity 2021 Sep;54(9):1976-1988.e7

Department of RNA Biology and Neuroscience, Osaka University, Suita, Osaka 565-0871, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka 565-0871, Japan; The Genome Editing Research and Development Center, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address:

Mutations in the adenosine-to-inosine RNA-editing enzyme ADAR1 p150, including point mutations in the Z-RNA recognition domain Zα, are associated with Aicardi-Goutières syndrome (AGS). Here, we examined the in vivo relevance of ADAR1 binding of Z-RNA. Mutation of W197 in Zα, which abolished Z-RNA binding, reduced RNA editing. Read More

View Article and Full-Text PDF
September 2021

Adenosine-to-inosine editing of endogenous Z-form RNA by the deaminase ADAR1 prevents spontaneous MAVS-dependent type I interferon responses.

Immunity 2021 Sep;54(9):1961-1975.e5

Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK. Electronic address:

Nucleic acids are powerful triggers of innate immunity and can adopt the Z-conformation, an unusual left-handed double helix. Here, we studied the biological function(s) of Z-RNA recognition by the adenosine deaminase ADAR1, mutations in which cause Aicardi-Goutières syndrome. Adar1 mice, bearing two point mutations in the Z-nucleic acid binding (Zα) domain that abolish Z-RNA binding, displayed spontaneous induction of type I interferons (IFNs) in multiple organs, including in the lung, where both stromal and hematopoietic cells showed IFN-stimulated gene (ISG) induction. Read More

View Article and Full-Text PDF
September 2021

Long-term effect of conventional phosphate and calcitriol treatment on metabolic recovery and catch-up growth in children with PHEX mutation.

J Pediatr Endocrinol Metab 2021 Sep 16. Epub 2021 Sep 16.

Division of Medical Genetics, Department of Medical Genetics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Objectives: Hereditary hypophosphatemic rickets (HR) is conventionally treated with phosphate and calcitriol. Exploring genotype and phenotypic spectrum of X-linked hypophosphatemic rickets (XLHR), focusing on short-term, long-term, and pubertal impact of conventional treatment was aimed.

Methods: Sixteen patients from 12 unrelated families with HR were analyzed for phosphate regulating endopeptidase homolog X-linked ( mutation. Read More

View Article and Full-Text PDF
September 2021

Olfactory entry promotes herpesvirus recombination.

J Virol 2021 Sep 15:JVI0155521. Epub 2021 Sep 15.

School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.

Herpesvirus genomes show abundant evidence of past recombination. Its functional importance is unknown. A key question is whether recombinant viruses can outpace the immunity induced by their parents to reach higher loads. Read More

View Article and Full-Text PDF
September 2021

Conductive hearing loss in the Hyp mouse model of X-linked hypophosphatemia is accompanied by hypomineralization of the auditory ossicles.

J Bone Miner Res 2021 Sep 15. Epub 2021 Sep 15.

Department of Trauma and Orthopaedic Surgery, Division of Orthopaedics, University Medical Center Hamburg-Eppendorf; Hamburg, Germany.

X-linked hypophosphatemia (XLH) is a hereditary musculoskeletal disorder caused by loss-of-function mutations in the PHEX gene. In XLH, increased circulating fibroblast growth factor 23 (FGF23) levels cause renal phosphate wasting and low concentrations of 1,25-dihydroxyvitamin D, leading to an early clinical manifestation of rickets. Importantly, hearing loss is commonly observed in XLH patients. Read More

View Article and Full-Text PDF
September 2021

PLA2G6 mutations cause motor dysfunction phenotypes of young-onset dystonia-parkinsonism type 14 and can be relieved by DHA treatment in animal models.

Exp Neurol 2021 Sep 11;346:113863. Epub 2021 Sep 11.

College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. Electronic address:

Parkinson's disease (PD), the most common neurodegenerative motor disorder, is currently incurable. Although many studies have provided insights on the substantial influence of genetic factors on the occurrence and development of PD, the molecular mechanism underlying the disease is largely unclear. Previous studies have shown that point mutations in the phospholipase A2 group VI gene (PLA2G6) correlate with young-onset dystonia-parkinsonism type 14 (PARK14). Read More

View Article and Full-Text PDF
September 2021

A Naturally-Occurring Point Mutation in a Hyaluronidase Gene () of UAMS-1 Results in Reduced Enzymatic Activity.

Can J Microbiol 2021 Sep 14. Epub 2021 Sep 14.

National Center for Toxicological Research, 4136, Microbiology, 3900 NCTR Road, Jefferson, Arkansas, United States, 72079-9502;

Hyaluronic acid is a high molecular weight polysaccharide that is widely distributed in animal tissues. Bacterial hyaluronidases degrade hyaluronic acid as secreted enzymes and have been shown to contribute to infection. UAMS-1 is a clinical isolate that codes for two hyaluronidases ( and ). Read More

View Article and Full-Text PDF
September 2021

Superresolution microscopy reveals photoreceptor-specific subciliary location and function of ciliopathy-associated protein, Cep290.

JCI Insight 2021 Sep 14. Epub 2021 Sep 14.

Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States of America.

Mutations in the cilium-associated protein CEP290 cause retinal degeneration as part of multi-organ ciliopathies or as retina-specific diseases. The precise location and the functional roles of CEP290 within cilia and, specifically, the connecting cilia (CC) of photoreceptors, remain unclear. We used superresolution fluorescence microscopy and electron microscopy (TEM) to localize CEP290 in the CC and in primary cilia of cultured cells with sub-diffraction resolution, and to determine effects of CEP290 deficiency in three mutant models. Read More

View Article and Full-Text PDF
September 2021

Shortening of membrane lipid acyl chains compensates for phosphatidylcholine deficiency in choline-auxotroph yeast.

EMBO J 2021 Sep 14:e107966. Epub 2021 Sep 14.

Membrane Biochemistry & Biophysics, Bijvoet Center for Biomolecular Research and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands.

Phosphatidylcholine (PC) is an abundant membrane lipid component in most eukaryotes, including yeast, and has been assigned multiple functions in addition to acting as building block of the lipid bilayer. Here, by isolating S. cerevisiae suppressor mutants that exhibit robust growth in the absence of PC, we show that PC essentiality is subject to cellular evolvability in yeast. Read More

View Article and Full-Text PDF
September 2021

The genetics of cardiac amyloidosis.

Heart Fail Rev 2021 Sep 13. Epub 2021 Sep 13.

Henry Ford Hospitals, 2799 W. Grand Blvd, K14 Cardiology, Detroit, MI, 48202, USA.

Heritable cardiac amyloidosis (CA) is an underrecognized cause of morbidity and mortality in the USA. It results from the accumulation of the misfolded protein transthyretin within the myocardium, resulting in amyloid transthyretin-associated cardiomyopathy (ATTR-CM). Over 150 different pathologic point mutations within the transthyretin gene have been identified, each carrying variable clinical phenotypes and penetrance. Read More

View Article and Full-Text PDF
September 2021

Off-target effects of base editors: what we know and how we can reduce it.

Curr Genet 2021 Sep 13. Epub 2021 Sep 13.

Research Centre for Medical Genetics, 1, Moskvorechye str., Moscow, 115522, Russian Federation.

The recently discovered CRISPR-Cas9 modification, base editors (BEs), is considered as one of the most promising tools for correcting disease-causing mutations in humans, since it allows point substitutions to be edited without generating double-stranded DNA breaks, and, therefore, with a significant decrease in non-specific activity. Until recently, this method was considered the safest, but at the same time, it is quite effective. However, recent studies of non-specific activity of BEs revealed that some of them lead to the formation of a huge number of off-targets in both DNA and RNA, occurring due to the nature of the Cas9-fused proteins used. Read More

View Article and Full-Text PDF
September 2021

Importance of twitching and surface-associated motility in the virulence of .

Virulence 2021 12;12(1):2201-2213

Departament De Genètica I Microbiologia, Facultat De Biociènces, Universitat Autònoma De Barcelona, Barcelona, Spain.

is a pathogen of increasing clinical importance worldwide, especially given its ability to readily acquire resistance determinants. Motile strains of this bacterium can move by either or both of two types of motility: (i) twitching, driven by type IV pili, and (ii) surface-associated motility, an appendage-independent form of movement. strain MAR002 possesses both twitching and surface-associated motility. Read More

View Article and Full-Text PDF
December 2021

DMRT1: An Ancient Sexual Regulator Required for Human Gonadogenesis.

Sex Dev 2021 Sep 1:1-14. Epub 2021 Sep 1.

Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, USA.

Transcriptional regulators related to the invertebrate sexual regulators doublesex and mab-3 occur throughout metazoans and control sex in most animal groups. Seven of these DMRT genes are found in mammals, and mouse genetics has shown that one, Dmrt1, plays a crucial role in testis differentiation, both in germ cells and somatic cells. Deletions and, more recently, point mutations affecting human DMRT1 have demonstrated that its heterozygosity is associated with 46,XY complete gonadal dysgenesis. Read More

View Article and Full-Text PDF
September 2021

Design of a FAIR digital data health infrastructure in Africa for COVID-19 reporting and research.

Adv Genet (Hoboken) 2021 Jun 11;2(2):e10050. Epub 2021 Jun 11.

Stanford Center for Biomedical Informatics Research Stanford University Stanford California USA.

The limited volume of COVID-19 data from Africa raises concerns for global genome research, which requires a diversity of genotypes for accurate disease prediction, including on the provenance of the new SARS-CoV-2 mutations. The Virus Outbreak Data Network (VODAN)-Africa studied the possibility of increasing the production of clinical data, finding concerns about data ownership, and the limited use of health data for quality treatment at point of care. To address this, VODAN Africa developed an architecture to record clinical health data and research data collected on the incidence of COVID-19, producing these as human- and machine-readable data objects in a distributed architecture of locally governed, linked, human- and machine-readable data. Read More

View Article and Full-Text PDF

Consistent B Cell Receptor Immunoglobulin Features Between Siblings in Familial Chronic Lymphocytic Leukemia.

Front Oncol 2021 26;11:740083. Epub 2021 Aug 26.

Laboratory Medical Immunology, Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, Netherlands.

Key processes in the onset and evolution of chronic lymphocytic leukemia (CLL) are thought to include chronic (antigenic) activation of mature B cells through the B cell receptor (BcR), signals from the microenvironment, and acquisition of genetic alterations. Here we describe three families in which two or more siblings were affected by CLL. We investigated whether there are immunogenetic similarities in the leukemia-specific immunoglobulin heavy (IGH) and light (IGL/IGK) chain gene rearrangements of the siblings in each family. Read More

View Article and Full-Text PDF

High Variability in Cellular Proliferation, Gene Expression, and Cytokine Production in the Nonneoplastic Colonic Epithelium of Young Mice.

Front Oncol 2021 27;11:705562. Epub 2021 Aug 27.

Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, United States.

An urgent need exists to identify efficacious therapeutic preventive interventions for individuals who are at high risk of developing colorectal cancer. To maximize the benefits of preventive intervention, it is vital to identify the time interval during which the initiation of a preventive intervention will lead to an optimal outcome. The goal of the present study was to determine if oncogenic events can be detected in the nonneoplastic colonic mucosa of mice prior to formation of the first adenoma, thus defining an earlier point of intervention along the cancer continuum. Read More

View Article and Full-Text PDF